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 Previous Article

Molecular and Cellular Biology, October 2008, p. 6134-6147, Vol. 28, No. 19
0270-7306/08/$08.00+0     doi:10.1128/MCB.00495-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Posttranscriptional Regulation of Chicken ccn2 Gene Expression by Nucleophosmin/B23 during Chondrocyte Differentiation{triangledown} ,{dagger}

Yoshiki Mukudai,1 Satoshi Kubota,2 Harumi Kawaki,2 Seiji Kondo,2 Takanori Eguchi,2 Kumi Sumiyoshi,2 Toshihiro Ohgawara,2,3 Tsuyoshi Shimo,3 and Masaharu Takigawa1,2*

Biodental Research Center, Okayama University Dental School,1 Department of Biochemistry and Molecular Dentistry,2 Department of Oral and Maxillofacial Surgery and Biopathological Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8525, Japan3

Received 26 March 2008/ Returned for modification 20 May 2008/ Accepted 17 July 2008

CCN2/CTGF is a multifunctional factor that plays a crucial role in the growth and differentiation of chondrocytes. The chicken ccn2 gene is regulated not only at the transcriptional level but also by the interaction between a posttranscriptional element in the 3' untranslated region (3'-UTR) and a cofactor. In the present study, we identified a nucleophosmin (NPM) (also called B23) as this cofactor. Binding of NPM to the element was confirmed, and subsequent analysis revealed a significant correlation between the decrease in cytosolic NPM and the increased stability of the ccn2 mRNA during chondrocyte differentiation in vivo. Furthermore, recombinant chicken NPM enhanced the degradation of chimeric RNAs containing the posttranscriptional cis elements in a chicken embryonic fibroblast extract in vitro. It is noteworthy that the RNA destabilization effect by NPM was far more prominent in the cytosolic extract of chondrocytes than in that of fibroblasts, representing a chondrocyte-specific action of NPM. Stimulation by growth factors to promote differentiation changed the subcellular distribution of NPM in chondrocytes, which followed the expected patterns from the resultant change in the ccn2 mRNA stability. Therefore, the present study reveals a novel aspect of NPM as a key player in the posttranscriptional regulation of ccn2 mRNA during the differentiation of chondrocytes.

* Corresponding author. Mailing address: Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8525, Japan. Phone: 81-86-235-6645. Fax: 81-86-235-6649. E-mail: takigawa{at}md.okayama-u.ac.jp

{triangledown} Published ahead of print on 4 August 2008.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, October 2008, p. 6134-6147, Vol. 28, No. 19
0270-7306/08/$08.00+0     doi:10.1128/MCB.00495-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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